The background of the present disclosure is hereinafter introduced with the discussion of techniques relating to its context. However, even when this discussion refers to documents, acts, artifacts and the like, it does not suggest or represent that the discussed techniques are part of the prior art or are common general knowledge in the field relevant to the present disclosure.
Medical imaging is a well-established technique (in the field of equipment for medical applications), which allows analyzing a body-part of a patient in a substantially non-invasive manner. A specific medical imaging technique is based on the administration of an ultrasound contrast agent (UCA) to the patient (for example, comprising a suspension of phospholipid-stabilized gas-filled microbubbles); the contrast agent acts as an efficient ultrasound reflector, so that it provides a corresponding enhancement in images of a body-part of the patient that are acquired by means of an ultrasound scanner.
The contrast agent may also be adapted to reach a specific (biological) target (for example, expressed in a lesion) and then to remain immobilized thereon. Particularly, in Ultra-Sound Molecular Imaging (USMI) techniques this result is achieved by using a (molecularly) targeted contrast agent that is formulated for attaching to the corresponding target (for example, by incorporating a ligand in its formulation capable of interacting with inflammatory or tumoral tissues). The detection of the targeted contrast agent that is immobilized allows identifying its target (for example, the corresponding lesion that would otherwise be difficult to discover); moreover, the quantification of this immobilized (targeted) contrast agent allows determining a condition of the target (for example, in therapeutic follow-up of the lesion).
However, the identification of the contribution of the immobilized contrast agent in the enhancement of the images, or Targeted Enhancement (TE), is hindered by the fact that only a small fraction of the targeted contrast agent actually reaches the target and remains immobilized thereon, whereas the rest of the targeted contrast agent instead continues to circulate for quite a long time (up to 10-30 min.), for example, until it is filtered out by the lungs and/or in the liver of the patient; therefore, until most of this circulating (targeted) contrast agent has disappeared, it is not possible to discriminate the immobilized contrast agent from the circulating contrast agent.
A common approach for detecting the immobilized contrast agent at an early stage after administration of the targeted contrast agent is a Differential Targeted Enhancement (dTE) technique. In this case, destructive pulses with high mechanical index (MI) are applied to the body-part so as to destroy most of the (immobilized and circulating) targeted contrast agent. Images acquired before the application of the destructive pulses (and then comprising the contribution of both the immobilized contrast agent and the circulating contrast agent) are filtered by subtracting images acquired after a short delay (of typically 30-90 s) from the application of the destructive pulses (and then mainly comprising the contribution of the circulating contrast agent only), so as to mainly preserve the contribution of the immobilized contrast only. However, in this way it is not possible to image the body-part again to detect the immobilized contrast agent since it has been destroyed by the application of the destructive pulses.
Alternatively, WO-A-2007/054544 (the entire disclosure of which is herein incorporated by reference) proposes processing the images to reduce a contribution of the circulating contrast agent by substantially suppressing (or at least attenuating) pixel values of the images showing high variations over time (at the same time preserving the pixel values showing low variations over time). For this purpose, the images are filtered by applying a modified Minimum Intensity Projection (Min_IP) algorithm, wherein each pixel value is replaced by the minimum among the pixel value itself and the corresponding pixel value in one or more preceding images.
However, a residual contribution of the circulating contrast agent may still be present in the images so filtered due to an incomplete suppression thereof. The residual contribution of the circulating contrast agent may degrade a conspicuity of the immobilized contrast agent, and then hamper the detection and especially the accurate quantification thereof.
The residual contribution of the circulating contrast agent generally has relatively low intensity. Therefore, a common approach for suppressing (or at least reducing) the residual contribution of the circulating contrast agent is thresholding the filtered images by resetting their pixel values lower than an amplitude threshold to zero; for example, in WO-A-2007/054544 the amplitude threshold is set to 0-5% of an allowable maximum of the pixel values.
However, this operation may have undesirable effects. Particularly, if the amplitude threshold is too low the thresholding of the filtered images may be ineffective in reducing the residual contribution of the circulating contrast agent (for example, in case of high gain and/or high dynamics of the ultrasound scanner or of high concentration of the targeted contrast agent); conversely, if the amplitude threshold is too high the thresholding of the filtered images may reduce the contribution of the immobilized contrast agent as well (for example, in case of low gain and/or low dynamics of the ultrasound scanner or of low concentration of the targeted contrast agent).
All of the above hinders the clinical application of medical imaging techniques based on the use of targeted contrast agents.